RT Journal Article T1 Evolution shapes the responsiveness of the D-box enhancer element to light and reactive oxygen species in vertebrates A1 Pagano, Cristina A1 Siauciunaite, Rima A1 Idda, María L. A1 Ruggiero, Gennaro A1 Ceinos Caride, Rosa María A1 Pagano, Martina A1 Frigato, Elena A1 Bertolucci, Cristiano A1 Foulkes, Nicholas S A1 Vallone, Daniela K1 2401.13 Fisiología Animal K1 3105 Peces y Fauna Silvestre K1 2411 Fisiología Humana AB The circadian clock is a highly conserved cell-autonomous mechanism that directs daily rhythms in most aspects of biology. Daily entrainment by environmental signals, notably light, is essential for its function. However, our understanding of the mechanisms and the evolution of photic entrainment remains incomplete. Fish represent attractive models for exploring how light regulates the circadian clock due to the direct light sensitivity of their peripheral clocks. Central to this property is the light induced expression of clock genes that is mediated by D-box enhancer elements. Here, using zebrafish cells, we reveal that the light responsive D-box enhancer serves as a nuclear target for reactive oxygen species (ROS). We demonstrate that exposure to short wavelengths of visible light triggers increases in ROS levels via NADPH oxidase activity. Elevated ROS activates the JNK and p38 MAP kinases and in turn, induces clock gene expression via the D-box. In blind cavefish and mammals, where peripheral clocks are no longer entrained by direct illumination, ROS levels are still increased upon light exposure. However, in these species ROS no longer induces D-box driven clock gene transcription. Thus, during evolution, alterations in ROS-responsive signal transduction pathways underlie fundamental changes in peripheral clock photoentrainment. PB Scientific Reports SN 20452322 YR 2018 FD 2018-09-04 LK http://hdl.handle.net/11093/4323 UL http://hdl.handle.net/11093/4323 LA eng NO Scientific Reports, 8(1): 13180 (2018) NO Universidad de Ferrara | Ref. FAR2014–2017 DS Investigo RD 08-feb-2025